Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis

Macrophages destroy pathogens and diseased cells through Fcγ receptor (FcγR)-driven phagocytosis of antibody-opsonized targets. Phagocytosis requires activation of multiple FcγRs, but the mechanism controlling the threshold for response is unclear. We developed a DNA origami-based engulfment system...

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Autores principales:	Nadja Kern, Rui Dong, Shawn M Douglas, Ronald D Vale, Meghan A Morrissey
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	Phagocytosis Antibody DNA origami immunotherapy Fc Receptor synthetic biology Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/22326acb213c44e0bb2e15c5800764e0
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id	oai:doaj.org-article:22326acb213c44e0bb2e15c5800764e0
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spelling	oai:doaj.org-article:22326acb213c44e0bb2e15c5800764e02021-11-30T14:34:38ZTight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis10.7554/eLife.683112050-084Xe68311https://doaj.org/article/22326acb213c44e0bb2e15c5800764e02021-06-01T00:00:00Zhttps://elifesciences.org/articles/68311https://doaj.org/toc/2050-084XMacrophages destroy pathogens and diseased cells through Fcγ receptor (FcγR)-driven phagocytosis of antibody-opsonized targets. Phagocytosis requires activation of multiple FcγRs, but the mechanism controlling the threshold for response is unclear. We developed a DNA origami-based engulfment system that allows precise nanoscale control of the number and spacing of ligands. When the number of ligands remains constant, reducing ligand spacing from 17.5 nm to 7 nm potently enhances engulfment, primarily by increasing efficiency of the engulfment-initiation process. Tighter ligand clustering increases receptor phosphorylation, as well as proximal downstream signals. Increasing the number of signaling domains recruited to a single ligand-receptor complex was not sufficient to recapitulate this effect, indicating that clustering of multiple receptors is required. Our results suggest that macrophages use information about local ligand densities to make critical engulfment decisions, which has implications for the mechanism of antibody-mediated phagocytosis and the design of immunotherapies.Nadja KernRui DongShawn M DouglasRonald D ValeMeghan A MorrisseyeLife Sciences Publications LtdarticlePhagocytosisAntibodyDNA origamiimmunotherapyFc Receptorsynthetic biologyMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Phagocytosis Antibody DNA origami immunotherapy Fc Receptor synthetic biology Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	Phagocytosis Antibody DNA origami immunotherapy Fc Receptor synthetic biology Medicine R Science Q Biology (General) QH301-705.5 Nadja Kern Rui Dong Shawn M Douglas Ronald D Vale Meghan A Morrissey Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis
description	Macrophages destroy pathogens and diseased cells through Fcγ receptor (FcγR)-driven phagocytosis of antibody-opsonized targets. Phagocytosis requires activation of multiple FcγRs, but the mechanism controlling the threshold for response is unclear. We developed a DNA origami-based engulfment system that allows precise nanoscale control of the number and spacing of ligands. When the number of ligands remains constant, reducing ligand spacing from 17.5 nm to 7 nm potently enhances engulfment, primarily by increasing efficiency of the engulfment-initiation process. Tighter ligand clustering increases receptor phosphorylation, as well as proximal downstream signals. Increasing the number of signaling domains recruited to a single ligand-receptor complex was not sufficient to recapitulate this effect, indicating that clustering of multiple receptors is required. Our results suggest that macrophages use information about local ligand densities to make critical engulfment decisions, which has implications for the mechanism of antibody-mediated phagocytosis and the design of immunotherapies.
format	article
author	Nadja Kern Rui Dong Shawn M Douglas Ronald D Vale Meghan A Morrissey
author_facet	Nadja Kern Rui Dong Shawn M Douglas Ronald D Vale Meghan A Morrissey
author_sort	Nadja Kern
title	Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis
title_short	Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis
title_full	Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis
title_fullStr	Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis
title_full_unstemmed	Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis
title_sort	tight nanoscale clustering of fcγ receptors using dna origami promotes phagocytosis
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/22326acb213c44e0bb2e15c5800764e0
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_version_	1718406492661481472

Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis

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